Phenylamino pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

  1. Luiz Claudio Ferreira PimentelORCID Logo,
  2. Lucas Villas Boas Hoelz,
  3. Henayle Fernandes Canzian,
  4. Frederico Silva Castelo BrancoORCID Logo,
  5. Andressa Paula de Oliveira,
  6. Vinicius Rangel CamposORCID Logo,
  7. Floriano Paes Silva Júnior,
  8. Rafael Ferreira Dantas,
  9. Jackson Antônio Lamounier Camargos Resende,
  10. Anna Claudia Cunha,
  11. Nubia BoechatORCID Logo and
  12. Mônica Macedo Bastos

Submitting author affiliation: Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil

Beilstein Arch. 2021, 202144. https://doi.org/10.3762/bxiv.2021.44.v1

Published 09 Jun 2021

  • Preprint

Abstract

The enzyme tyrosine kinase Bcr-Abl-1 is the main molecular target in the treatment of chronic myeloid leukemia and can be competitively inhibited by tyrosine kinase inhibitors such as imatinib. New potential competitive inhibitors were synthesized using the phenylamino pyrimidine pyridine (PAPP) group as a pharmacophoric fragment, and these compounds were biologically evaluated. The synthesis of the twelve new compounds was performed in three steps and assisted by microwave irradiation in a 1,3-dipolar cycloaddition to obtain 1,2,3-triazole derivatives substituted on carbon C-4 of the triazole nucleus. All of them had their inhibitory activities evaluated against a chronic myeloid leukemia cell line (K562) that expresses the enzyme tyrosine kinase Bcr-Abl-1 and against healthy cells (WSS-1) to observe their selectivity. Three compounds had promising results, showing an IC50 between 1.0 and 7.3 mM, and were subjected to molecular docking studies. This result suggests that such compounds can interact at the same binding site as imatinib, probably sharing a competitive inhibition mechanism. One of them showed the greatest interaction affinity for Bcr-Abl-1 in the docking studies.

Keywords: chronic myeloid leukemia; 1,3-dipolar cycloaddition; imatinib; phenylamino pyrimidine pyridine; 1,2,3-triazole.

Supporting Information

Format: DOCX Size: 7.4 MB   Download

How to Cite

When a peer-reviewed version of this preprint is available, this information will be updated in the information box above. If no peer-reviewed version is available, please cite this preprint using the following information:

Pimentel, L. C. F.; Hoelz, L. V. B.; Canzian, H. F.; Branco, F. S. C.; de Oliveira, A. P.; Campos, V. R.; Júnior, F. P. S.; Dantas, R. F.; Resende, J. A. L. C.; Cunha, A. C.; Boechat, N.; Bastos, M. M. Beilstein Arch. 2021, 202144. doi:10.3762/bxiv.2021.44.v1

Download Citation
Download RIS (Reference Manager) Download BIB (BIBTEX)

© 2021 Pimentel et al.; licensee Beilstein-Institut.
This is an open access work under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0). Please note that the reuse, redistribution and reproduction in particular requires that the author(s) and source are credited and that individual graphics may be subject to special legal provisions.
The license is subject to the Beilstein Archives terms and conditions: (https://www.beilstein-archives.org/xiv/terms)

Other Beilstein-Institut Open Science Activities

Logo
Logo
Logo
Symposia